Klotho Neurosciences Advances Manufacturing of ALS Gene Therapy KLTO-202

Analysis reveals significant industry trends and economic implications

Release Date

2025-06-30

Category

Clinical Trial Event

Reference

Source

Breakthrough Clinical Results

Klotho Neurosciences announced it is progressing with manufacturing and process development for KLTO-202, a gene therapy targeting amyotrophic lateral sclerosis (ALS). KLTO-202 utilizes a neuroprotective RNA splice variant of the alpha-Klotho gene (s-KL), shown to have favorable therapeutic outcomes in animal models. The company anticipates completing manufacturing and process development in eight months, followed by FDA meetings, animal safety studies, IND filing, and site preparation. Phase I/II clinical trials in ALS patients are projected to begin in the third quarter of the following year. The company will leverage contract research organizations (CROs) to manage manufacturing and clinical trials.

Key Highlights

  • Klotho Neurosciences is advancing manufacturing of KLTO-202, a gene therapy for ALS.
  • KLTO-202 leverages a neuroprotective RNA splice variant of the alpha-Klotho gene (s-KL).
  • Preclinical studies in animal models showed favorable therapeutic outcomes.
  • Phase I/II clinical trials are expected to start in Q3 of the following year.

Incidence and Prevalence

Global ALS Incidence and Prevalence Estimates

Incidence Rates by Region

The annual incidence rate of ALS varies significantly across different regions globally:

Prevalence

Ethnic Variations

Ethnic variations in ALS incidence have been consistently observed:

Age and Gender Patterns

Genetic Factors

Key Unmet Needs and Target Populations for ALS

Unmet Medical Needs

Pre-symptomatic detection and intervention represents a critical unmet need in ALS care. Research indicates that understanding the pre-symptomatic phase could "transform our understanding of key events in pathogenesis" and "dramatically accelerate progress towards disease prevention." Related to this is the need for improved biomarkers that are "critically important to studying pre-symptomatic ALS and essential to efforts to intervene therapeutically before clinically manifest disease emerges."

Despite significant research advances, the exact cause of ALS remains largely unknown. Translational challenges persist with "challenges to be overcome in order to achieve improved success rates for translating drugs from animal models to clinics for treating ALS." This highlights the need for novel preclinical protocol standards, potentially combining "animal models with human induced pluripotent stem cells (iPSCs)" to improve translational success.

Many healthcare systems, including Germany, may not be able to meet the complex needs of patients with ALS (pwALS) because non-medical services such as psychological support or social counselling are not regularly included in their care. Specialised neuropalliative care is not routinely implemented nor widely available. There is also a need for standardized quality of life measures, as "there is limited consensus regarding which are most valid, reliable, responsive, and interpretable."

Challenges remain in delivering RNA-based therapeutics to the central nervous system, and there is a clear need for assistive devices designed for ALS patients with limited upper extremity strength who are not confined to a wheelchair.

Target Populations

Research suggests distinct treatment approaches may be needed for different ALS subtypes: - Spinal-onset ALS (sALS) patients show gut-dysbiosis associated with disease severity - Bulbar-onset ALS (bALS) patients display oral-dysbiosis linked to symptom severity

These findings "support distinct microbial mechanisms underlying two ALS subtypes, which have been previously grouped together as a single disease."

Genetic factors affecting survival remain understudied, with research noting "a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS." Recent studies have identified specific genes associated with shorter survival, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR: 1.8), highlighting the need for genotype-specific approaches.

At-risk carriers of ALS-associated genetic variants need "paradigms for providing appropriate clinical care" including genetic testing protocols, monitoring for early signs, and lifestyle recommendations. Increased access to predictive genetic counseling in a timely manner is a significant need given potential access to gene-specific therapies in the presymptomatic stage.

DNA methylation regulation represents an emerging target, with research showing "rare variants in the TET2 gene" significantly increase ALS risk (OR = 1.95).

Caregivers of pwALS are also highly burdened, but there is still a lack of support services for them.

Current clinical trials, such as the TUDCA-ALS study, are targeting general ALS populations with add-on therapies to riluzole, while regulatory agencies are evaluating gene-specific therapies like Qalsody (Tofersen) for SOD1-associated ALS, highlighting the potential of gene-targeted therapies for specific genetic subgroups.

Drug used in other indications

KLTO-202 Clinical Trials Information

Based on the available information, there is no data regarding a drug or compound called "KLTO-202" being trialed for ALS or any other indications. The information about this compound, its clinical trials, intervention models, dosing regimens, or administration protocols is not present in the provided context.

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